NCT02129881

Brief Summary

A study to assess cell therapy as a treatment to prevent kidney transplant rejection. The trial will involve purification of naturally occurring regulatory T cells (nTregs) from living-donor renal transplant recipients. The cells will then be grown in the laboratory and re-infused into the patient five days after the kidney transplant. This trial is part of an international European Union funded consortium aimed at evaluating cellular immunotherapy in solid organ transplantation (The ONE Study). It is anticipated that immune regulation induced by nTreg therapy can eventually be used to recude the need for conventional immunosuppression in transplant recipients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2014

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2014

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 1, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 2, 2014

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 23, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 23, 2017

Completed
Last Updated

January 25, 2019

Status Verified

January 1, 2019

Enrollment Period

3 years

First QC Date

May 1, 2014

Last Update Submit

January 24, 2019

Conditions

End-stage Renal Failure

Outcome Measures

Primary Outcomes (1)

  • Incidence of biopsy-confirmed acute rejection.

    60 weeks

Secondary Outcomes (8)

  • Time to first acute rejection episode

    60 weeks

  • Severity of acute rejection episodes

    60 weeks

  • Total immunosuppressive burden

    60 weeks

  • Incidence of chronic graft dysfunction

    60 weeks

  • Incidence of graft loss through rejection

    60 weeks

  • +3 more secondary outcomes

Study Arms (1)

Autologous regulatory T Cell Product

EXPERIMENTAL

Autologous regulatory T Cell Product (1-10 million cells/kg) infused intravenously 5 days post renal transplantation. Recipients also receive prednisolone, mycophenolate mofetil, and tacrolimus as detailed below: Prednisolone Day 0: 500 mg IV (250mg pre-op, 250mg intra-op) Day 1: 125 mg IV Day 2 to 14: 20.0 mg/day oral Week 3 to 4: 15.0 mg/day oral Week 5 to 8: 10.0 mg/day oral Week 9 to 12: 5.0 mg/day oral Week 13 to 14: 2.5 mg/day oral Week 15 to End: Cessation Mycophenolate Mofetil (MMF) Day -7 to -2: 500 mg/day oral Day -1 to 14: 2000 mg/day oral Week 3 to 36: 1000 mg/day oral Week 37 to 40: 750 mg/day oral Week 41 to 44: 500 mg/day oral Week 45 to 48: 250 mg/day oral Week 49 to End: Cessation Tacrolimus Day -4 to 14: 3-12 ng/ml oral Week 3 to 12: 3-10 ng/ml oral Week 13 to 36: 3-8 ng/ml oral Week 37 to End: 3-6 ng/ml oral

Biological: Autologous regulatory T Cell Product

Interventions

Autologous regulatory T Cell ProductBIOLOGICAL

Autologous regulatory T Cell Product (1-10 million cells/kg) infused intravenously 5 days post renal transplantation. Recipients also receive prednisolone, mycophenolate mofetil, and tacrolimus as detailed in the arm description.

Autologous regulatory T Cell Product

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor
  • Aged at least 18 years
  • Able to commence the immunosuppressive regimen at the protocol-specified time point
  • Willing and able to participate in The ONE Study IM and HEC subprojects
  • Signed and dated written informed consent

You may not qualify if:

  • Patient has previously received any tissue or organ transplant
  • Known contraindication to the protocol-specified treatments / medications
  • Genetically identical to the prospective organ donor at the HLA loci (0-0-0 mismatch)
  • PRA grade \> 40% within 6 months prior to enrolment
  • Previous treatment with any desensitisation procedure (with or without IVIg)
  • Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin)
  • Evidence of significant local or systemic infection
  • EBV-negative; serologically positive for anti-HIV-1,2; HBsAg; Anti-HBc; Anti-HCV-ab; Anti-HTLV-1,2 or syphilis (Treponema palladium)
  • Significant liver disease, defined as persistently elevated AST and/or ALT levels \> 2 x ULN (Upper Limit of Normal range)
  • Malignant or pre-malignant haematological conditions
  • Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
  • Any condition which, in the judgement of the Investigator, would place the subject at undue risk
  • Ongoing treatment with systemic immunosuppressive drugs at study entry
  • Participation in another clinical trial during the study or within 28 days prior to planned study entry
  • Female patients of child-bearing potential with a positive pregnancy test at enrolment
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Oxford Transplant Centre - Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (2)

  • McCallion O, Cross AR, Brook MO, Hennessy C, Ferreira R, Trzupek D, Mulley WR, Kumar S, Soares M, Roberts IS, Friend PJ, Lombardi G, Wood KJ, Harden PN, Hester J, Issa F. Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants. Med. 2025 May 9;6(5):100561. doi: 10.1016/j.medj.2024.11.014. Epub 2024 Dec 27.

    PMID: 39731908DERIVED

  • Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Boger CA, Scotta C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Ollinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyo J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 May 23;395(10237):1627-1639. doi: 10.1016/S0140-6736(20)30167-7.

    PMID: 32446407DERIVED

Related Links

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, ChronicRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Giovanna Lombardi, PhD

    King's College Hospital NHS Trust

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 1, 2014

First Posted

May 2, 2014

Study Start

April 1, 2014

Primary Completion

March 23, 2017

Study Completion

March 23, 2017

Last Updated

January 25, 2019

Record last verified: 2019-01

Locations

GB(2)